Systematic search method

Finding the minimum of the hybrid energy function is very complex. Similar to the protein folding problem, the number of degrees of freedom is far too large to allow a complete systematic search in all variables. Systematic search methods need to reduce the problem to a few degrees of freedom (see, e.g.. Ref. 30). Conformations of the molecule that satisfy the experimental bounds are therefore usually calculated with metric matrix distance geometry methods followed by optimization or by optimization methods alone. 

Overall there are 2n — n — 1 = 1013 variations of different two-, three-, four- up to the only one possible ten-component reaction mixture. From these 1013 different combinations of starting materials, several gave the expected and known MCR products. Using a minimum peak height requirement of 30% (compared to the sum of all peaks in the respective LC chromatogram) for a novel and unknown reaction product, unique MCR products were found. For example, the expected Ugi 4-CR product was re-found by this systematic search method (Figure 10.1). 

A number of groups have successfully used these and similar ideas to enable the systematic search method to be applied to quite large molecules. 

Systematic search methods attempt to sample all of the possible conformations of a ligand by incrementing the torsional angles of each rotatable bond. Unfortunately, this technique is computationally expensive due to the exponential increase in the number of possible conformations (Mconr) as the number of rotatable bonds... 

Perhaps the most commonly utilized systematic search method is incremental construction, which is used by DOCK [41], FlexX [42], E-Novo [91], LUDI [45, 46], ADAM [92], and TrixX [93]. In this particular method, the ligand is... 

Event clustering Besides event location, spatial and/or temporal clustering of events can be systematically investigated. Therefore, we developed a systematic search method for spatially and temporally clustered events which was applied on AE events in mines and laboratory measurements. 

The purpose of the HARA is to find all foreseeable hazards of an item by applying a systematic search method, and to rate the hazards on a scale of Automotive Safety Integrity Levels (ASILs) from A (lowest) to D (highest), or to rate them as not specifically safety-critical (QM = normal Quality Management is considered sufficient to cope with them). 

Using amplitude ratios makes inverting for source mechanisms more difficult, however, because a ratio is a nonlinear function of its denominator. Systematic searching methods still work, but because the dimensionality of the model space is increased by two over that for a DC mechanism, the computational labor is greatly increased (typically by a factor of more than 100). 

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